Research Article Details
| Article ID: | A20975 |
| PMID: | 25607821 |
| Source: | Oncol Rep |
| Title: | Hepatic expression of the Sptlc3 subunit of serine palmitoyltransferase is associated with the development of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis. |
| Abstract: | The molecular mechanisms underlying the progression of nonalcoholic steatohepatitis (NASH) have not been fully elucidated. The aim of this study was to identify factors involved in NASH progression by analysis of pathophysiological features and gene-expression profiles in livers of STAM mice, a model of NASH-associated hepatocarcinogenesis. C57BL/6N (B6N) mice were injected with streptozotocin to generate STAM mice. Four-week-old male STAM and B6N mice were fed a high-fat diet (HFD) (STAM-F, B6N-F) or a conventional diet (STAM-C, B6N-C) until they were 10, 14, or 18 weeks old. Blood glucose and nonalcoholic fatty liver disease (NAFLD) activity scores of STAM-F were higher than those of STAM-C during all observation periods. STAM-F mice had more severe hepatic fibrosis at 14 weeks, and exhibited higher levels of α-fetoprotein-positive hepatic tumor formation with multiplication than STAM-C mice at 18 weeks. At 14 weeks, cDNA microarray analysis revealed that the hepatic expression of eight mRNAs was ≥30-fold higher in STAM-F than B6N-F mice. The expression of another four genes was increased ≥5-fold in STAM-F than B6N-F mice, and ≥5-fold in B6N-F relative to B6N-C mice. Of the 12 genes, the difference in Sptlc3 mRNA expression was most pronounced, and gradually increased over time, as determined by quantitative RT-PCR in STAM-F mice. In addition, Sptlc3 mRNA expression in STAM-F mice was higher than that in db/db mice that received HFD and in B6N mice fed a choline‑deficient L-amino acid (CDAA)-defined diet. In conclusion, a high-fat diet aggravated pathophysiological findings in the liver in NASH mouse models, and the hepatic expression of Sptlc3 mRNA was potentially associated with NASH progression. |
| DOI: | 10.3892/or.2015.3745 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D075 | Choline | Supplement | DB00122 | PLD2 product of; PLD1 product of | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |